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Vol. 38 No. 9 (2026): Vol 38 Issue 9 Year 2026

Copyright (c) 2026 Venkatesh Reddycherla

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This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis of New Indole-Pyrazole linked Isoxazoles as Potent Antibacterial and Antibiofilm Agents

https://doi.org/10.14233/ajchem.2026.36375
Venkatesh Reddycherla
Department of Chemistry, Sathyabama Institute of Science and Technology (Deemed University), Jeppiaar Nagar, Chennai-600119, India; Center for Nanoscience and Nanotechnology, Sathyabama Institute of Science and Technology (Deemed University), Jeppiaar Nagar, Chennai-600119, India
https://orcid.org/0009-0001-3725-7657
K. Chennakesavulu
Department of Chemistry, Sathyabama Institute of Science and Technology (Deemed University), Jeppiaar Nagar, Chennai-600119, India
https://orcid.org/0000-0002-3415-1865
G. Ramanjaneya Reddy
Department of Chemistry, Sathyabama Institute of Science and Technology (Deemed University), Jeppiaar Nagar, Chennai-600119, India
https://orcid.org/0000-0001-5509-0873
R. Bhaskar Reddy
Department of Chemistry, Sathyabama Institute of Science and Technology (Deemed University), Jeppiaar Nagar, Chennai-600119, India
https://orcid.org/0009-0000-7154-2315

Corresponding Author(s) : Venkatesh Reddycherla

venkateshtsp@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 9 (2026): Vol 38 Issue 9 Year 2026

Abstract

A series of new indole-pyrazole-linked isoxazole hybrids (5a-o) were synthesized using Cu(I)-catalyzed 1,3-dipolar cycloaddition and assessed for antibacterial and antibiofilm activities against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) pathogens. Biological evaluation showed that the dihalogenated derivatives, particularly 3,5-dichloro (5g) and 2,4-dichloro (5i), exhibited pronounced antibacterial activity comparable to dicloxacillin. Both compounds substantially inhibited biofilm formation. Molecular docking studies against penicillin-binding protein (PDB ID: 1MWT) supported the experimental findings, with favourable binding interactions and high predicted affinity. Structure-activity relationship analysis indicated that dichloro substitution enhanced antibacterial potency. These hybrid compounds may serve as potential candidates for further investigation against resistant Staphylococcus aureus infections.

Keywords

Antibacterial Biofilm Indole Isoxazoles Pyrazole Molecular docking
(1)
Reddycherla, V.; Chennakesavulu, K.; Reddy, G. R.; Reddy, R. B. Synthesis of New Indole-Pyrazole Linked Isoxazoles As Potent Antibacterial and Antibiofilm Agents. ajc 2026, 38, 2438-2446.
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References
  1. C.P. Pandhurnekar, H.C. Pandhurnekar, A.J. Mungole, S.S. Butoliya and B.G. Yadao, J. Heterocycl. Chem., 60, 537 (2023); https://doi.org/10.1002/jhet.4586.
  2. G.J. Martis and S.L. Gaonkar, RSC Adv. 15, 8213 (2025); https://doi.org/10.1039/d4ra08339c
  3. Y.R. Girish, K.S.S. Kumar, H.S. Manasa and S. Shashikanth, J. Chin. Chem. Soc., 61, 1175 (2014); https://doi.org/10.1002/jccs.201400170
  4. T.R. Swaroop, K.S. Sharath Kumar, M. Palanivelu, S. Chaitanya and K.S. Rangappa, J. Heterocycl. Chem., 51, 1866 (2014); https://doi.org/10.1002/jhet.1864
  5. H. Ananda, K.S. Sharath Kumar, M. Nishana, M. Srivastava, M. Hegde, R. Byregowda, B. Choudhary, S.C. Raghavan and K.S. Rangappa, Mol. Cell. Biochem., 426, 149 (2017); https://doi.org/10.1007/s11010-016-2887-7
  6. H.R. Puneeth, H. Ananda, K.S.S. Kumar, K.S. Rangappa and A.C.S. Sharada, Med. Chem. Res., 25, 1842 (2016); https://doi.org/10.1007/s00044-016-1628-5
  7. S. Michael Marcy and J.O. Klein, Med. Clin. North Am., 54, 1127 (1970); https://doi.org/10.1016/S0025-7125(16)32582-2
  8. R.A. Al-Qawasmeh, M. Huesca, V. Nedunuri, R. Peralta, J. Wright, Y. Lee and A. Young, Bioorg. Med. Chem. Lett., 20, 3518 (2010); https://doi.org/10.1016/j.bmcl.2010.04.137
  9. A. Kumari and R.K. Singh, Bioorg. Chem., 89, 103021 (2019); https://doi.org/10.1016/j.bioorg.2019.103021
  10. F. Song, Z. Li, Y. Bian, X. Huo, J. Fang, L. Shao and M. Zhou, Arch. Pharm., 353, e2000143 (2020); https://doi.org/10.1002/ardp.202000143
  11. T. Meng, Y. Hou, C. Shang, J. Zhang and B. Zhang, Arch. Pharm., 354, e2000266 (2021); https://doi.org/10.1002/ardp.202000266
  12. F. Gao, L. Ye, F. Kong, G. Huang and J. Xiao, Bioorg. Chem., 91, 103162 (2019); https://doi.org/10.1016/j.bioorg.2019.103162
  13. V.P. Kumar, J. Renjitha, C.T. Fathimath Salfeena, K.T. Ashitha, S.K. Rangappa, V. Sunil and B.S. Sasidhar, Chem. Biol. Drug Des., 90, 703 (2017); https://doi.org/10.1111/cbdd.12990
  14. S. Narsimha, N.S. Kumar, B.K. Swamy, N.V. Reddy, S.K. Althaf Hussain and M.S. Rao, Bioorg. Med. Chem. Lett., 26, 1639 (2016); https://doi.org/10.1016/j.bmcl.2016.01.055
  15. K. Lewis, Cell, 181, 29 (2020); https://doi.org/10.1016/j.cell.2020.02.056
  16. H.F. Wertheim, M.C. Vos, A. Ott, A. van Belkum, A. Voss, J.A.J.W. Kluytmans, P.H.J. van Keulen, C.M.J.E. Vandenbroucke-Grauls, M.H.M. Meester and H.A. Verbrugh, Lancet, 364, 703 (2004); https://doi.org/10.1016/S0140-6736(04)16897-9
  17. T.E. Kehl-Fie, Y. Zhang, J.L. Moore, A.J. Farrand, M.I. Hood, S. Rathi, W.J. Chazin, R.M. Caprioli and E.P. Skaar, Infect. Immun., 81, 3395 (2013); https://doi.org/10.1128/IAI.00420-13
  18. N. Chandal, R. Kalia, A. Dey, R. Tambat, N. Mahey, S. Jachak and H. Nandanwar, Commun. Biol., 7, 1489 (2024); https://doi.org/10.1038/s42003-024-06996-8
  19. N. Ramu, T.M. Krishna, R. Kapavarapu and S. Narsimha, RSC Adv., 14, 8921 (2024); https://doi.org/10.1039/D3RA07509E
  20. Y. Jia, W. Chen, R. Tang, J. Zhang, X. Liu, R. Dong, F. Hu and X. Jiang, Cell Host Microbe, 31, 1101 (2023); https://doi.org/10.1016/j.chom.2023.06.008
  21. D. Carcione, J. Intra, L. Andriani, F. Campanile, F. Gon, S. Carletti, N. Mancini, G. Brigante, D. Cattaneo, S. Baldelli, M. Chisari, A. Piccirilli, S. Di Bella and L. Principe, Pharmaceuticals, 16, 1304 (2023); https://doi.org/10.3390/ph16091304
  22. H. Brüssow, Microb. Biotechnol., 17, e14510 (2024); https://doi.org/10.1111/1751-7915.14510
  23. M.H. Muhammad, A.L. Idris, X. Fan, Y. Guo, Y. Yu, X. Jin, J. Qiu, X. Guan and T. Huang, Front. Microbiol., 11, 928 (2020); https://doi.org/10.3389/fmicb.2020.00928
  24. K. Sauer, P. Stoodley, D.M. Goeres, L. Hall-Stoodley, M. Burmølle, P.S. Stewart and T. Bjarnsholt, Nat. Rev. Microbiol., 20, 608 (2022); https://doi.org/10.1038/s41579-022-00767-0
  25. A. Ali, A. Zahra, M. Kamthan, F.M. Husain, T. Albalawi, M. Zubair, R. Alatawy, M. Abid and M.S. Noorani, Microorganisms, 11, 1934 (2023); https://doi.org/10.3390/microorganisms11081934
  26. H. Parveen, S. Mukhtar, M.O. Albalawi, S. Khasim, A. Ahmad and M.Y. Wani, Pharmaceutics, 16, 1570 (2024); https://doi.org/10.3390/pharmaceutics16121570
  27. K. Qvortrup, L.D. Hultqvist, M. Nilsson, T.H. Jakobsen, C.U. Jansen, J. Uhd, J.B. Andersen, T.E. Nielsen, M. Givskov and T. Tolker-Nielsen, Front. Chem., 7, 742 (2019); https://doi.org/10.3389/fchem.2019.00742
  28. M.D. Bandgar, S. Peddapelli, R. Kapavarapu, J. Boruwa, S. Kavela and S. Narsimha, RSC Med. Chem., 16, 4154 (2025); https://doi.org/10.1039/D5MD00103J
  29. N. Ramu, T.M. Krishna, V. Nasipireddy, R. Kapavarapu and S. Narsimha, ChemistrySelect, 8, e202300777 (2023); https://doi.org/10.1002/slct.202300777
  30. E. Ramya Sucharitha, T.M. Krishna, R. Manchal, G. Ramesh and S. Narsimha, Bioorg. Med. Chem. Lett., 47, 128201 (2021); https://doi.org/10.1016/j.bmcl.2021.128201
  31. E.F. Haney, M.J. Trimble and R.E.W. Hancock, Nature Protocols, 16, 2615 (2021); https://doi.org/1038/s41596-021-00515-3
  32. S. Stepanović, D. Vuković, V. Holá, G. Di Bonaventura, S. Djukić, I. Ćirković and F. Ruzicka, APMIS, 115, 891 (2007); https://doi.org/10.1111/j.1600-0463.2007.apm_630.x
  33. T.V. Hansen, P. Wu and V.V. Fokin, J. Org. Chem., 70, 7761 (2005); https://doi.org/10.1021/jo050163b
  34. M.D.A.A. Pasha, E.R. Sucharitha, R. Kapavarapu, S. Narsimha, A. Dubba and K. Siddoju, ChemistrySelect, 10, e202504361 (2025); https://doi.org/10.1002/slct.202504361
  35. K. Premalatha, R. Kapavarapu, S.I. Al-Resayes, V. Nasipireddy, M. Azam, and S. Narsimha, ChemistrySelect, 9, e202401858 (2024); https://doi.org/10.1002/slct.202401858
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